TABLE 1.
Target protein | Camelid species/Synthetic library | sdAb nomenclature | Binding site | Activity | Application | References |
---|---|---|---|---|---|---|
Antithrombin | Llama | KB‐AT‐01 ‐ 07; KB‐AT‐23 | None defined | Neutralization of antithrombin function | Research/Therapy | 79 |
Factor VIIa | Llama | αFVIIa‐VHH | FVIIa protease domain | Detection of FVIIa but not FVII | Diagnostics | 75 |
Factor VIIa | Llama | KB‐FVIIa‐004 | FVIIa protease domain | Inhibits free FVIIa but not TF‐bound FVIIa activity | Research | 49 |
Factor XIIa | Llama | A10 | Catalytic domain | Binds selectively to α‐FXIIa | Research/Diagnostics | 52 |
Factor XIIa | Llama | B7 | Catalytic domain | Binds both α‐FXIIa and β‐FXIIa | Research/Diagnostics | 52 |
Fibrinogen | Dromedary | VFIB1, ‐2, ‐3 | None defined | High‐affinity binding to fibrinogen | Diagnostics | 76, 77 |
PAI‐1 | Alpaca | VHH‐s‐a98 | Surface loops around central β‐sheet A | Switches PAI‐1/PA to substrate pathway | Research | 105 |
PAI‐1 | Alpaca | VHH‐2w‐64 (Nb64) | Surface loops around central β‐sheet A | Switches PAI‐1/PA to substrate pathway | Research/Therapy | 60, 105 |
PAI‐1 | Alpaca | VHH‐s‐a27 | None defined | Neutralization of PAI‐1 function | Research | 105 |
PAI‐1 | Alpaca | VHH‐s‐a93 | Vicinity of reactive center loop | Interferes with initial PAI‐1/PA complex formation | Research | 105 |
PAI‐1 | Alpaca | VHH‐2g‐42 (Nb42) | Vicinity of reactive center loop | Interferes with initial PAI‐1/PA complex formation | Research/Therapy | 60, 105 |
PN‐1 | Synthetic library | KB‐PN1‐A08, ‐B11, ‐F06, ‐H12 | Reactive center loop | Neutralization of human and murine PN‐1 function | Research | 106 |
hTAFI | Alpaca | VHH‐TAFI‐i and VHH‐TAFI‐a series | None defined | Interfere with TAFI activation and/or activity | Research | 54, 55, 57 |
hTAFI | Alpaca |
VHH‐TAFI‐a51 VHH‐TAFI‐i103 |
None defined | Stimulate activity of TAFI zymogen | Research | 56 |
mTAFI | Alpaca | VHH‐TAFI‐i49 | Lys212 & Arg227 | Stimulates activity of TAFI zymogen | Research | 107 |
u‐PA | Alpaca | Nb4 | Active site | Inhibits u‐PA activity | Research | 59 |
u‐PA | Alpaca | Nb7 | 37s and 70s loops of the N‐terminal β‐barrel | Allosteric inhibitor of u‐PA activity | Research | 58 |
u‐PA | Alpaca | Nb22 | Active site | Inhibits u‐PA activity | Research | 58 |
VWF | Llama | ALX‐0081 (caplacizumab) | Human A1 domain | Inhibition of VWF/glycoprotein Ibα interaction | Therapy | 80, 82, 83 |
VWF | Llama | KB‐VWF‐006bv | Human/murine A1 domain | Inhibition of VWF/glycoprotein Ibα interaction | Research | 63, 64 |
VWF | Llama | AU‐VWFa‐11 | Human/murine A1 domain | Specifically detects platelet‐binding VWF conformation | Diagnostics | 66, 67, 69, 72, 73, 74 |
Abbreviations: hTAFI, thrombin‐activatable fibrinolysis inhibitor; mTAFI, murine thrombin‐activatable fibrinolysis inhibitor; PA, plasminogen activator; PAI‐1, plasminogen activator inhibitor‐1; PN‐1, protease nexin‐1; u‐PA, urokinase plasminogen activator; TAFI, thrombin‐activatable fibrinolysis inhibitor; VWF, von Willebrand factor.